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Pharmacological Treatment Of Attention Deficit Disorders By Jay Tarnow, M.D., and Nancy L. Eisenberg, MSW, LCSW, LMFT 

Since medication is frequently used in the treatment of ADHD, it is important to have reasonable expectations regarding its effectiveness and to be aware of potential side effects.

General Medication Information

• Each person responds uniquely to medication.
• Medications in children are very safe.  More studies have been done about children taking stimulant medications than any other medications including nonprescription drugs. Prescribed and taken correctly, they are not addictive.  Individuals do not have a physical craving for medication.  When stimulant medication is out of the blood stream, the individual goes back to exhibiting full-blown ADHD symptoms.
• Both hyperactive and nonhyperactive individuals with attentional problems can benefit from medications.
• Medication is effective for 54% of nonhyperactive children and 80-90% of hyperactive children.
• Medications are prescribed for adults with ADHD in the same small dosages given to children.
• When taking the appropriate dosage, medication usually doesn't affect personality.
• Dosages should never be changed without discussion with the prescribing doctor.

Medication Does Not:

• cure ADHD.
• teach the ADHD individual how to cope and compensate for difficulties.
• imply a "magic pill".
• just treat hyperactivity.  Medication also helps with impulsivity, attention difficulties, and aggression.
• cause addiction.  Long-term studies show that children who have taken stimulant medication are not more prone to substance abuse but rather, less so.
• have a permanent effect on a child's growth, if carefully monitored and weight is not effected.
• sedate children so that their behavior improves.
• lead to aggressive, dangerous behavior.
• create personality changes.
• cause seizures.
• cause tics but may bring them out in patients with Tourette's Disorder.  Stimulants may increase the tics.

Medication Does:

• treat ADHD symptoms.
• influence long-term progress and prognosis of ADHD children, when utilized in conjunction with treatment modalities specific for ADHD.
• stimulate the attention center of the brain to function more normally.
• affect impulsivity, attention and behavior positively.  More specifically, stimulants can increase attention span, concentration and compliance; improve handwriting and fine motor skills; and allow improved peer relationships.  Also, a decrease in impulsivity, aggressiveness, and hyperactivity can occur.

Medications Frequently Used IN TREATING ADHD

I.Psychostimulants: 

Psychostimulants stimulate the release of norepinephrine and dopamine from the nerve terminals in the attention center of the brain.  Of the pharmacologic options available for ADHD, stimulants are the most studied, most commonly used, most effective, and are usually the first used agents for treatment.

Stimulants Improve:

• Core Symptoms
• Inattention
• Impulsivity
• Hyperactivity

 AND

• Impulsive aggression
• Social interactions
• Academic productivity accuracy

Advantages of Stimulants:

• Specifically treat ADHD core symptoms of inattention, overactivity, and impulsiveness
• Largest effect on ADHD of any drug class, especially for children
• Significant benefit in 90% of ADHD if two or more tried in succession and titrated carefully
• Calms comorbid aggression and oppositional-defiant behavior
• Results of given dose seen immediately; relatively easy titration

Stimulant Side-effects (most common):

• Insomnia
• Loss of appetite
• Rebound of hyperactivity after medication wears off
• Irritability
• Stomachache
• Headache
• Over focusing, compulsive behaviors
• Weight loss

This is not a complete list of side effects and others may occur.  Tell your doctor about any unusual or bothersome side effect.

Signs of over dosage:

• Increased hyperactivity
• Overly obsessive behavior or anxiety
• Social withdrawal
• "Zombie-like" appearance or sedation
• Increased blood pressure and pulse

Potential Side Effects: 

• Proven safer than most psychiatric medications
• None of these side effects are dangerous for healthy children
• Side effects are usually experienced when medication is started and decrease over time
• Tics

  There is an increased risk that children will develop these symptoms if there is a familial predisposition to Tourette's Disorder.  Children who have undetected Tourette's may develop tics and the full-blown symptoms of the disorder.  Less than 5% have tics and the incidence of Tourette's is very rare.  Symptoms of Tourette's are more pronounced under stress.

• Appetite Suppression

  This may be more of a problem if medication is given before meals.  Appetite will usually return when the effects of the medication have worn off.  Approximately 50-60% complain of appetite loss; 50-60% of difficulties falling asleep; and 20-40% of stomach cramps and headaches when first starting the medication.  There may be mild increases in heart rate and blood pressure.  Mild weight loss may occur in the initial first or second month, but no overall effect on skeletal growth.  Rarely, children can experience a growth slow down if they continue to lose weight.  There are easy methods to deal with this such as adjusting medications, allowing time periods where appetite is not suppressed, and using protein drinks at bedtime.

• Behavioral Rebound

  Increased excitability, talkativeness, impulsivity, or insomnia may appear 5 to 20 hours after the last dose treatment.  Rebound resembles a return of the original symptoms after the medication wears off, except that the magnitude of symptoms actually increases above the baseline.  Rebound has been clearly demonstrated in normal children and has been described, but less well documented, as a clinical problem.

• Impaired Cognitive Performance

  Mainly observed at high doses and probably represents the toxicity of over medication.  Single doses of methylphenidate above 1mg/kg have been repeatedly found to impair cognitive functioning.  In predisposed children who may have Bipolar Disorder, psychotic or psychotic-like symptoms which include hallucinations or delusions, mania, stereotyped or compulsive behavior, and self-biting may occur.

• Neuropsychiatric Effects

  Include tics or other abnormal movements, night terrors, and lip-licking or biting.  Occasional adverse effects include dizziness, nausea, nightmares, constipation, lethargy, fatigue, anxiety, fearfulness, hypercusis (increased acuity of hearing), rash, hives, and a sensation of "ants crawling on skin."  However, these effects are uncommon.

Relative Contraindications:

• Amphetamines should not be used in patients with known psychosis, a history of symptoms suggestive of a risk for psychosis, or a history of substance abuse in an adolescent or adult patient, peers, or immediate family members without careful monitoring.  Other contraindications include a child with a family history of tics or Tourette's Disorder, cardiac abnormalities or high blood pressure abnormalities, seizure disorder, or severe side effects in a previous stimulant trial.

Psychostimulants Used in ADHD

Short Acting Duration Duration of effect in hours

Methylphenidate (Ritalin, Methylin) 1-4

Dextrophetamine (Dexedrine) 1-6

Dextroamphetamine (DextroStat) 1-6

Dexmethylphenidate (Focalin) 4-6

Intermediate Acting

Methylphenidate (Ritalin-LA) 4-8

Methylphenidate ER (Metadate ER, Methylin ER) 4-8

• Methylphenidate (Metadate CD) 6-8
• Pemoline (Cylert) 7-9
• Amphetamine-dextroamphetamine (Adderall) 6-8
• Dextroamphetamine (Dexadrine Spansule) 6-8
• Dextro-Methylphenidate (Focalin) 6

Long Acting

• Methylphenidate (Concerta) 10-12
• Amphetamine-dextroamphetamine (Adderall XR) 10-12
• Dextromethylphenidate XR (Focalin XR) 10-12
• Daytrana (Methylphenidate)  9-12
• Vyvanse Dextroamphetamine Prodrug 12

Adderall

• Capsules contain a mixture of different amphetamine salts
• Usually taken once a day; lasts 12 hours
• Dose is split into 2 separately timed releases which prevents a peak/valley effect
• Capsule
• A single product made up of 4 different amphetamine salts: Dextroamphetamine Sulfate, Dextroamphetamine Saccharate, Amphetamine Sulfate, and Amphetamine Aspartate. 
• Usually taken once or twice a day.

Adderall XR

• Capsules contain a mixture of different amphetamine salts
• Usually taken once a day; lasts 12 hours
• Dose is split into 2 separately timed releases which prevents a peak/valley effect
• Capsule may be opened and given as "sprinkles" for young children

Concerta

• Extended release formulation of methylphenidate which is designed to last 12 hours with just one dose
• Helps maintain focus without in-school and after-school dosing
• The medication is released gradually in a smooth pattern minimizing the peaks/valleys associated with short-acting medication
• Capsule may not be opened or broken

Daytrana

• A methylphenidate patch which works for about 10 hours
• It takes about 1-2 hours to start working 

• The patch gives more control to decide when to stop the stimulant effect or for children who have difficulty taking medication

Dexedrine or Dextrostat (Dextroamphetamine)

• Dexedrine spansule is given once per day. 50% of beads dissolve immediately and 50% in four hours
• Dexedrine/Dextrostat tablets can be taken two or three times a day

Metadate

• 10, 20, and 30mg extended-release methylphenidate capsule, which may be opened and used as "sprinkles"
• Offers extended-release strength of methylphenidate and may eliminate the need for midday dosing
• Effects last 8 hours which may be helpful because it covers the school day and may then wear off to improve appetite during after school hours
• A generic tablet is available

Focalin (dexmethylphenidate HCI)

• A refined filtered formulation of methylphenidate (dextrosteroisomer)
• Available in 2.5, 5, and 10mg tablets.  The recommended dose will be half the dose of Ritalin
• Taken twice daily
• Short-acting benefit is that the side effects should wear off quickly

Focalin XR

• Extended release capsule
• Comes in 5mg, 10mg, 15mg, 20mg capsules
• Dosing once per day in the morning with a 10-12 hour effect
• Capsule can be opened and sprinkled on food for children who cannot swallow pills
• Less side effects for ADHD and children with anxiety

Ritalin (Methylphenidate)

• Usually taken twice a day; a third dose may also be prescribed to help the child participate in after-school activities, do homework, and interact with the family
• Also available in sustained release form, Ritalin SR or Ritalin LA, which is taken once in the morning eliminating the need for a noon dose

Vyvanse (Dextroamphetamine)

• New delivery system. Dextroamphetamine is attached to the amino acid Lysine. In the stomach Peptidase an enzyme that digests food separates the medication and makes it available for absorption into the blood stream. This offers a smoother blood level than Adderall XR. The other advantage is that this medication cannot be snorted or injected, thereby decreases it's potential for abuse.
• Dosing once daily in AM.

• Capsule can be opened and powder mixed with liquid for children who cannot swallow pills. This also allows making varying doses by amount of solution given.

II. Non Stimulant

Strattera (atomoxetine) A Selective Norepinephrine Reuptake Inhibitor

• Dosing 1 or 2 times per day
• Relatively mild side effects
• No life threatening side effects
• May cause slight (1-3mm) rise in blood pressure, which is equal to stimulants
• 2 cases of liver reactions

Most common side effects:

• Sedation/Insomnia
• Nausea
• Decreased appetite for first month in 15% of cases
• Tremor
• Blurry vision
• Itching

This is not a complete list of side effects and others may occur.  Tell your doctor about any unusual or bothersome side effect.

III. Tricyclic Antidepressants

Elavil (Amitriptyline)

Pamelor (Nortriptyline)

Norpramin (Desipramine)

Tofranil (Imipramine)

Common Characteristics of these older medications:

• Prescribed for ADHD children who are also experiencing anxiety and/or enuresis.
• Elicits mild improvements in attention and activity level, and decreased impulsivity, irritability, aggressiveness, and temper outburst
• May be given 1-3 times a day
• May become less effective over time
• May improve sleep onset

Side Effects:

Side effects are numerous, including cardiac side effects such as irregular heartbeat, dry mouth, sedation, and hypertension or hypotension

This is not a complete list of side effects and others may occur.  Tell your doctor about any unusual or bothersome side effect.

MEDICATIONS USED IN TREATING COMORBID DISORDERS WITH ADHD

Other Medications:

These medications are considered "3rd line".  They are often prescribed when the other more commonly used medications have proven ineffective or if special problems or comorbid conditions exist that are associated with ADHD.

I. SSRIs-Antidepressants (no evidence of effectiveness in ordinary ADHD)

Brand Generic

Prozac (Floxetine)

Luvox(Fluvoxamine)

Remeron (Mirtazapine)

Lexapro (Escitalopram Oxalate)

Paxil (Paroxetine)

Zoloft (Sertraline)

ADHD children and adolescents may get agitated and sometimes more hyperactive at high doses (greater than 150mg).

Dosing:

• Usually once a day
• Don't need blood levels
• Fewer side effects than tricyclic antidepressants
• Not lethal in overdose
• Don't interfere with heart function

Adverse Effects:

• Nausea, vomiting, upset stomach
• Insomnia
• Agitation
• Restlessness
• Weight loss
• Sexual dysfunction 
  

This is not a complete list of side effects and others may occur.  Tell your doctor about any unusual or bothersome side effect.

II. (SSRI and SNRI) Selective Norepinephrine Reuptake Inhibitor

• Effexor (Venlafaxine)

  Preliminary reports in adults indicate that Effexor may be useful in decreasing ADHD symptoms, particularly in ADHD adults who are also experiencing anxiety and/or depression.  These preliminary reports have not held up in research

• Cymbalta (Duoxetine)

Common side effects include:

• Nausea, somnolence, dry mouth, dizziness, constipation, nervousness, increased sweating and sexual dysfunction

Uncommon side effect:

• Increased blood pressure (greater chance of occurrence at dosages above 200mg/day), blood pressure will normalize with dose reduction

This is not a complete list of side effects and others may occur.  Tell your doctor about any unusual or bothersome side effect.

III. Antidepressant (Dopamine Reuptake Inhibitor)

 Wellbutrin (Bupropion)

• Antidepressant unrelated to all the others
• Central nervous system stimulant effects
• More frequently prescribed for ADD adults
• Contraindicated in patients with seizure disorder, bulimia, or anorexia nervosa
• Usually given once a day (XR) or twice a day (SR)

Common side effects include:

• Agitation, dry mouth, insomnia, headache/migraine, nausea, vomiting, constipation, and tremor

Uncommon side effects include:

• Seizures (4/1000), swelling, chest pain, shortness of breath, liver damage, urinary symptoms, lack of coordination, hypertension

This is not a complete list of side effects and others may occur.  Tell your doctor about any unusual or bothersome side effect.

IV. Mood Stabilizers

Tegretol or Carbatrol (Carbamazepine)

• The most responsive symptoms include Bipolar Disorder, aggressive behaviors, low frustration tolerance, and impulsivity
• Usually given 2-3 times a day

Common side effects include:

• Stomachaches, dizziness, sedation, blurred vision and low blood count.  A complete blood count should be done periodically especially when patient has repeated or severe infections

Adverse effects:

• Upset stomach
• Nausea, vomiting
• Decreased white blood cell count, if gets fever, sore throat, infection, may   need to consider agranulocytosis (medical emergency involving stopping Tegretol)
• Rash
• Avoid in pregnancy
• Sedation
• Weight gain
• Ataxia
• Hair loss
• Low platelet count
• Chemical Hepatitis
• Pancreatitis

This is not a complete list of side effects and others may occur.  Tell your doctor about any unusual or bothersome side effect.

Monitoring:

• Needs blood levels and CBC monitoring

Dosing:

• Begin 200mg BID to TID up to 1500mg or so based on blood levels

Toxicity:

• Drowsiness, ataxia, muscle weakness, confusion
• Avoid in pregnancy

Valproic Acid (Depacote)

Gabapentin (Neurontin)

Lamitrogene (Lamictal)

Topamax

Adverse effects:

• Mild drowsiness, dizziness, or weakness
• Headache
• Diarrhea, constipation, or upset stomach (nausea)
• Depression, anxiety, or other emotional changes
• Sleep problems
• Changes in menstrual periods
• Enlarged breasts
• Tremor (shaking)
• Hair loss
• Weight changes
• Vision changes
• Unusual or unpleasant taste in your mouth

This is not a complete list of side effects and others may occur.  Tell your doctor about any unusual or bothersome side effect.

V. Atypical Anti-pyschotics

Abilify (Aripiprazole)Approved for children

Geodon (Ziprasidone)

Seroquel (Quetiapine)

Risperdal (Risperidone Approved for children

Zyprexa (Olanzapine)

Common Characteristics:

• Prescribed for the management of manifestations of Schizophrenia, Bipolar Disorder

• Improves a full range of psychotic symptoms including positive symptoms, negative symptoms, uncontrolled hostility/excitement, and disorganized thought
• Usually given 2-3 times a day
• Has been shown to improve impulsive aggression in children and adolescents  May also improve sleep and symptoms associated with severe anxiety and depression
• Helps tics, severe Obsessive Compulsive Disorder
• Risperdal and Abilify helpful in Autistic Spectrum Disorder

Common side effects include:

• Sedation, dizziness, constipation, nausea, indigestion, runny nose, rash, and rapid heartbeat

Uncommon side effects include:

• Restlessness, tremors, involuntary slow or jerky facial or body movements (Tardive Dykinesia), and muscle stiffness 
  

This is not a complete list of side effects and others may occur.  Tell your doctor about any unusual or bothersome side effect.

VI. Neuroleptics

Haldol

Prolixin

Thorazine

Mellaril

Adverse Effects

• Blurred vision, dry mouth, constipation, urinary retention, decreased sweating, memory impairment, impotence, increased heart rate
• Drowsiness, weight gain, low blood pressure
• Skin rashes
• Photosensitive
• Lowered seizure threshold
• Restlessness
• Muscle stiffness, tightness, abnormal motor movements (Tardive Dyskinesia-usually involves mouth first)
• Neuroleptic malignant hypertension (medical emergency severs rigidity, change in mental status, abnormal vital signs-increased temperature, autonomic instability)

Toxicity

• Sedation
• Low blood pressure
• Extrapyramidal Symptoms (muscle stiffness, rigidity, abnormal motor  movements)

This is not a complete list of side effects and others may occur.  Tell your doctor about any unusual or bothersome side effect.

VII. Catapres (Clonidine) or Tenex (Guanfacine)

• May be prescribed for ADHD children who have difficulty with aggression, impulsivity, insomnia, and/or severe hyperactivity
• May have a sedation effect
• Is utilized with Tourette 's syndrome and ADHD children with tics
• Usually taken up to 3-4 times a day
• A 5-day patch is available for Clonidine called Catapress TTS
• Targets hyperactivity and impulsivity more than attention
• Not approved for children – Clonidine
• Guanfacine recently approved for children

Common side effects include:

• Dry mouth, irregular heart rate, hypotension, headache and dizziness, stomachache, and vomiting

Uncommon side effects include:

• Depression, nightmares, anxiety and rebound hypertension if patient suddenly stops taking the medication

This is not a complete list of side effects and others may occur.  Tell your doctor about any unusual or bothersome side effect.

VIII. Provigil (Modafinil)

• Used in Narcolepsy
• Stimulant effects on the brain
• Not approved for children
• Not approved for ADHD
• Some people with ADHD have benefit without effects on blood pressure or pulse

There are other medications, diets and chemical, herbal products that have been tried or are being investigated for their use in the treatment of ADHD symptoms. A physician who is familiar with the treatment of ADHD in children, adolescents, and adults should be consulted for medication and treatment decisions.

Jay Dennis Tarnow, M.D., and Nancy L. Eisenberg, MSW, LCSW, LMFT

Revised May 2009